Asymmetric dimethylarginine: a novel marker of risk and a potential target for therapy in chronic kidney disease.
OBJECTIVE
Asymmetric dimethylarginine (ADMA) is a naturally occurring amino acid that reduces the bioavailability of nitric oxide. ADMA opposes important antiatherosclerotic effects of nitric oxide. ADMA not only correlates with traditional and nontraditional risk factors but is also considered a common pathway mediating the adverse vascular effects of traditional and nontraditional risk factors. Over the past 15 years, ADMA has generated increasing interest from both clinical scientist and basic researchers. The present study summarizes the latest developments in the field.


RESULTS
Modulating (increasing) activity of dimethylamine dimethylaminohydrolase, the main enzyme metabolizing ADMA, emerges as a possible therapeutic option to lower ADMA and favorably influence organ dysfunction. These preclinical findings are thought to be of major importance as ADMA predicts cardiovascular events and mortality in the general population and in patients with chronic kidney disease. Also, ADMA uniformly predicts the progression of moderate and severe chronic kidney disease. Symmetrical dimethylarginine, the structural isomer of ADMA, which was mistakenly thought to be without biological relevance, indicates the degree of renal impairment.


CONCLUSIONS
ADMA also beautifully explains many facets of the pathophysiology of chronic kidney disease. Future preclinical and especially clinical studies are required to prove the importance of ADMA in renal and cardiovascular disease.
Kielstein
Jan T
JT
Division of Nephrology, Department of Internal Medicine, Medical School Hannover, Germany. Kielstein@yahoo.com
Zoccali
Carmine
C
D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D018450:Disease Progression; D015316:Genetic Therapy / Q000379:methods; D005919:Glomerular Filtration Rate; D013006:Growth Hormone / Q000627:therapeutic use; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D009765:Obesity / Q000150:complications / Q000378:metabolism; D012307:Risk Factors; D012720:Severity of Illness Index; D016896:Treatment Outcome
D015415:Biomarkers; C018524:N,N-dimethylarginine; D013006:Growth Hormone; D001120:Arginine; D000581:Amidohydrolases; C059999:dimethylargininase